The cutaneous radiation syndrome. A disorder of the cutaneous communication network?

The effects of ionizing radiation, both wanted and unwanted, on regenerating tissues such as skin have traditionally exclusively been attributed to anti-proliferative activity on presumptive stem cells. The detailed mechanisms leading to clinical effects such as early erythema or late fibrosis remained largely unrevealed. In recent years this concept has been modified considerably, based on information primarily obtained by application of immunological and molecular biological methods. Concomitantly, our understanding of the skin organ as a complicated, both initiator and effector organ of the systemic immune response has enlarged dramatically, demonstrating a complex cutaneous intra- and intercellular communication network including pro- and anti-inflammatory cytokines and their receptors, adhesion molecules and surface antigens. These components regulate among others the interaction between epidermal and dermal cells, as well as microvascular endothelial cells, the latter representing the interface between the circulating immunocompetent cells (granulocytes, lymphocytes, etc) and the skin. Increasing evidence has been obtained that ionizing radiation modulates this network in a refined manner, involving transcriptional activation of immediate early (TNF-α, IL-1, -5, -6, -8, ICAM-1) as well as late (EGF-R, TGF-β responding genes. Though resembling other inflammatory conditions of the skin, a specific time and dose-dependant pattern after radiation exposure evolves, allowing a distinct discrimination between the effects of high and low single doses as well as fraction. This enlarged concept of the cutaneous radiation reaction offers new options for causal-oriented treatment with biological response modifiers including steroids and other immuno-suppressants as well as cytokines and receptor antagonists, as well as definition of optimal time windows for initiation and termination of therapeutic intervention. (author)